Cell Elasticity-based Microfluidic Label-free Isolation of Metastatic Tumor Cells

Abstract

Aims: Circulating tumor cells (CTCs) have significant diagnostic value for cancer patients. We report a label-free, simple and rapid microchannel filter type device for isolation of known metastatic cancer cells based on their mechano-physical properties like size and deformability. Study Design: Metastatic renal cancer cells were highly elastic and squeezed through microchannels much smaller than their size. Using a reverse-selectivity approach, the number of microchannels and their dimensions were varied to optimize and reduce the shear stress on tumor cells such that these did not pass through filtering channels. Place and Duration of Study: Department of Electrical Engineering and Department of Bioengineering, University of Texas at Arlington, USA, between June 2012 and March 2013. Methodology: A microfluidic filter type device was fabricated using soft lithography in polydimethylsiloxane (PDMS). The device consistedof one inlet and one outlet connected via 400 microchannels. First of all human derived renal cancer cells were suspended in 1X PBS solution and passed through these microchannels and capture efficiency of the device was calculated. The dimensions of microchannels were varied in order to increase efficiency. Eventually cancer cells were spiked in rat blood and isolated from the mixture. Results: For different dimensions of microchannels capture efficiencies of the devices were calculated. First device consisted of microchannels of 20 µm x 10 µm (Device-1) and the capture efficiency was 31.04±2.5%. Then dimensions were varied to 10 µm x 10 µm (Device-2), 10 µm x 5 µm (Device-3), and 5 µm x 5 µm (Device-4) and capture efficiencies increased to 45.18±1.85%, 70.96±2.39% and 78.36±4.29%, respectively. Rat blood was used as negative control in Device-3 and Device-4 and blood cells were able to pass the microchannels. Finally renal cancer cells were spiked in rat blood and isolated from red blood cells and white blood cells. Conclusion: A novel microdevice is fabricated to detect metastatic renal cancer cells based on their size and deformability. The efficiency of the device is more than 78%. This microfluidic channel device does not require preprocessing of blood (except dilution) or tagging/modification of cells and can be implemented for primary screening of cancer.